An established kidney cell line (MDCK) contains an adenylate cyclase system sensitive to the effects of glucagon, vasopressin, isoproterenol and prostaglandin E1. We have found that the effects of the peptide hormones were selectively lost or reduced in a cloned line derived from MDCK cells transformed by Harvey murine sarcoma virus. Isoproterenol and prostaglandin E1 responses were unchanged. Glucagon sensitivity can be restored by including butyrate in the culture medium or by prolonged culture in a chemically-defined medium containing hormone supplements. Disappearance and reappearance of glucagon receptors seem to be responsible for the loss and restoration of glucagon sensitivity. The study of this system will provide an understanding of the cellular regulation of hormone receptors, their response and the biochemical pathway leading to the appearance of hormone receptors.